We have recently demonstrated that infusion of insulin and glucagon strikingly enhances survival of mice with a fulminant murine hepatitis. The possible therapeutic implications of these findings justify further research directed towards consolidating and expanding the initial observations, and towards probing the mechanisms through which hormonal effects are implicated. We plan to employ in vitro and in vivo model systems to investigate the means by which insulin and glucagon may influence the cource of liver cell injury and repair. With these model systems, we will attempt to confirm and more clearly define the protective effects of insulin and glucagon noted in our previous studies and extend our prior observations regarding the enhancing effect of hormone treatment upon the repair process in both toxic and viral induced liver cell injury. We will seek out the mechanisms, both cellular and molecular, through which insulin and glucagon produced the effects described. By probing experimental models at least some of which respond dramatically to infusions of these two pancreatic hormones, we are attempting to define the physiological mechanisms that regulate certain aspects of liver function and growth. An important aspect of this study, however is to find whether or not one might reasonably expect that these two hormones do benefit diseased or damaged liver in clinical situations, and if so, what kind of injury might respond.